The present invention relates to dental products comprising cyclodextrins and hydrogen peroxide.
Dental plaque is present to some degree, in the form of a film, on virtually all dental surfaces. It is a by-product of microbial growth, and comprises a dense microbial layer consisting of a mass of micro-organisms embedded in a polysaccharide matrix. The micro-organisms present in plaque are mainly coccoidal organisms, particularly in early plaque. As plaque ages and matures, gram negative anaerobes and filamentous organisms appear and become more common after a few days. Plaque itself adheres to dental surfaces and may not be removed completely even with a rigorous brushing regimen and can build up, for example, in recessed areas of tooth surfaces, such as approximal regions and fissures. Moreover, plaque rapidly reforms on the tooth surface after it is removed.
Plaque may form on any part of the tooth surfaces, and can be found particularly at the gingival margin, in pits and fissures in the enamel, and on the surface of dental calculus. The danger associated with the formation of plaque on the teeth lies in the tendency of plaque to build up and eventually contribute to gingivitis, periodontitis and other types of periodontal disease, as well as dental caries and dental calculus.
More specifically, dental plaque is a precursor to the formation of the hard crystalline build up on teeth referred to as dental calculus. Both the bacterial and the non-bacterial components of plaque mineralize to form calculus, which comprises mineralized bacteria as well as organic constituents, such as epithelial cells, live bacteria, salivary proteins, leukocytes, and crystalline substances containing both calcium and phosphorous, e.g., hydroxyapatite, Ca.sub.10 (PO.sub.4).sub.6 (OH).sub.2, octacalcium phosphate, Ca.sub.8 (HPO.sub.4).sub.2 (PO.sub.4).sub.4. 5H.sub.2 O, brushite, CaHPO.sub.4-.2H.sub.2 O, and whitlockite, which is considered to have the formula .beta.-Ca.sub.3 (PO.sub.4).sub.2. Dental plaque and, hence, calculus are particularly prone to form at the gingival margin, i.e., the junction of the tooth and gingiva. The buildup of plaque at, and below, the gingival margin is believed to be the prime cause of gingivitis and periodontal disorders.
Mouthwashes have been formulated to contain antimicrobial ingredients whose function is to reduce the buildup of plaque, either by the direct bactericidal action (i.e. killing) on plaque and salivary micro-organisms and by bacteriostatic action (i.e. growth inhibition) on plaque and salivary micro-organisms. Scheie, A. AA. (1989) Modes of Action of Currently Known Chemical Anti-Plaque Agents Other than Chlorhexidine. J. Dent. Res. 68 Special Issue: 1609-1616.
However phenolics useful in oral compositions have low aqueous solubilities which limit their use in oral compositions and they require high levels of either 1) alcohol; 2) surfactants; or 3) co-solvents or combinations of the above for sufficient solubility in the carrier. PCT Appln No. WO 94/16674.
For example, thymol has been used as a anthelmintic and antiseptic, in mouthwashes containing a combination of menthol, methyl salicylate, eucalyptol and thymol. Oral compositions including mouthwashes and dentifrices containing phenolic compounds are referred to in U.S. Pat. No. 4,945,087; WO 94/16.16,674; WO 94/07477; and WO 94/18939. Triclosan (2,4,4'-trichloro-2'-hydroxydiphenyl ether) is a phenolic, nonionic antimicrobial agent used in various soap and toiletry products. In the oral care area, triclosan has been used as a plaque-inhibitory agent in various toothpastes and mouthrinses. Oral composition including triclosan are referred to in the following: U.S. Pat. Nos. 4,892,220; 5,032,386; 5,037,637; 5,034,154; 5,080,887; 5,236,699; 5,043,154; 5,032,385; and 5,156,835 as well as EPO 85303216.7.
Cyclodextrins are known to form inclusion complexes with various compounds. The cyclodextrin molecule consists of glucopyranose units arranged in a torus-like or donut-like configuration having all the secondary hydroxyl groups located on one side of the torus and all primary hydroxyl groups located on the other side. Alpha, beta, and gamma cyclodextrin contain 6, 7 & 8 cyclic glucopyranose units, respectively, in the torus shell. The "lining" of the internal cavity is formed by hydrogen and glucosidic oxygen-bridge atoms and therefore the surface is slightly apolar.
Hydrogen peroxide has been used in oral compositions, for example, in U.S. Pat. Nos. 4,431,631; 4,537,778; 4,684,517; 5,104,644; 5,174,990; 5,186,926; 5,296,216 and 5,310,546, and PCT International Application WO 97/26855. Hydrogen peroxide and other peroxygens including carbamide peroxide, sodium percarbonate and sodium perborate have been used for treating certain oral disorders such as, oral malodor, dental plaque, gingivitis, aphthous ulcers and for controlling post-surgical infections and the like.
Hydrogen peroxide and other peroxygens tend to be unstable with storage, although this can be reduced at acidic pHs, and that interaction of peroxygens with other excipients in oral formulations can cause their degradation. In particular, certain flavors, including peppermint, spearmint and citrus flavors are known to be unstable in the presence of peroxygens (See, U.S. Pat. No. 4,537,778). Also flavor ingredients such as menthofurane and flavor terpenes are unstable or can react with peroxygens. In U.S. Pat. No. 5,186,926 it is stated that menthol has some slight susceptibility to oxidation and preferably should not be formulated with a peroxygen compound. Also, methyl salicylate can hydrolyze in aqueous solutions. To overcome these incompatibility and degradation problems, numerous solutions have been proposed: 1) Using dual-phase packaging to isolate coreactive ingredients into separate compartments (U.S. Pat. Nos. 4,528,180; 4,849,213; 5,186,926); 2) Physical encapsulation of the peroxygen or the peroxide-sensitive excipient to protect against degradation by co-reactive ingredients.
We have found that these degradation problems can be greatly reduced, without the need for dual-phase packaging or physical encapsulation, by using soluble cyclodextrins described in detail below. When incorporated into the composition at the correct amount, the soluble cyclodextrins form inclusion complexes with the flavor or phenolic compounds protecting them from rapid degradation from the peroxygen co-ingredients. Thus, this invention stabilizes formulations which use peroxygens together with flavor/phenolic compounds within the same hydroalcoholic/aqueous composition. We have found that combinations of peroxygens with phenolic antimicrobials formulated in oral compositions are especially effective, with respect to bactericidical activity, against a broad spectrum of oral micro-organisms. However, until this invention, there was no easy way to formulate these ingredients into a single-phase, stable, aqueous composition.